The major thrust of current investigations into the use of radiolabeled monoclonal antibodies (MAbs) is focused on the development of their applications in imaging and therapy. Evidence suggests that Tc-99m possess ideal characteristics for imaging and Re-186 for therapy. However, the procedures for labeling MAbs with these radionuclides remain, inefficient and cumbersome. Unless the labeling processes are made simple, efficient, and reliable, the use of MAbs will continue to be restricted. MAbs have a variety of groups for radionuclide labeling. However, only one group can be used with this mode of labeling MAbs with Tc-99m and Re-186. Investigations with this mode of labeling MAbs with Tc-99 have shown less than satisfactory results and the chemistry is unclear. Our hypothesis calls for important improvements in two prominent steps of this mode of radiolabeling. Based on this hypothesis, we have developed a technique that allows us to consistantly label MAb (IgM) with TC-99m with > 95% efficiency. The method is simple, does not require purification and has potential for Re-196 labeling as well as for adaption to a much preferred "kit" type of preparation. Preliminary results indicate that the Tc-99m MAb preparation is stable upon incubation with DTPA, human serum and cysteine. The immunospecificity of the protein as determined by specific antigen interaction assay is also unchanged. The purpose of this proposal is to fully investigate the feasibility of this technique to label IgM, IgG and F(ab')2 fragments with Tc-99m and Re- 186, prepare a total of six prototype kits, and evaluate them systemically in vitro and in vivo. The stability of the labeled radionuclide when challenged with such agents as DTPA, human serum and cysteine in several fold excess molar ratios to the protein will be determined by ITLC and HPLC. Tissue distribution will be carried out in tumor bearing Balb-C mice and compared to that with the corresponding MAbs labeled with In-111 by administering both preparations to each animal and determining the concomitant radioactivity in dissected tissues with a high energy resolution, solid state Ge(Li) detector. Special attention will be given to the distribution in the tumor, liver, kidney, gut and plasma. The chemistry of labeling will be studied and its effects on the structural integrity and immunospecificity of MAbs will be examined using "tracer inhibition", spectrophotometric and gel electrophoretic techniques.